Lens

陳美如

臺北榮民總醫院
國立陽明交通大學醫學系
 Introduction

• The lens is a transparent, biconvex

structure behind the pupil and iris
• Small fibers called zonules are
attached to the capsule holding the
lens, suspending it from the eye wall
 Lens
• Refraction: the lens refract light to focus on the retina
(refractive index: 1.39, refractive power: 15~16 D)
• The lens changes shape to focus on objects close ->
accommodation: 7~8 D at 25 years old, 1~2 D at 50 years old
• The lens is more flat on its anterior side than on its posterior
side
 Embryology

https://obgynkey.com/ophthalmology/
Embryology
• Optic vesicle -> Optic cup
• A disc-shaped thickening of
Surface ectoderm over the
optic vesicle (Lens placode or
Lens plate)
• A small indentation (Lens pit)
-> a single layer of cuboidal cells
encased within a basement
membrane (lens capsule) -> Lens
vesicle
• Lens fibers -> Embryonic/fetal
nucleus
https://link.springer.com/chapter/10.1007/978-981-10-2627-0_1
Primary lens fibers
• Cells of posterior lens vesicle
rapidly elongate and obliterate the
lumen of the cavity by week 6 of
gestation
ØThe cells are called primary lens
fibers-> “embryonic nucleus”
• Cells of the anterior lens vesicle
remains cuboidal and form lens
epithelium -> subsequent growth
and differentiation

https://entokey.com/the-lens/
 Secondary lens fibers (I)

• Start from week 7 of gestation

• Primary lens fibers lose their nuclei
and other cellular organelles
• Anterior cells continue to divide ->
Pre-equatorial cells begin to form
secondary lens fibers - elongating
along the posterior surface of the
primary fibers
https://blogs.iu.edu/chenglab/research/
https://www.slideshare.net/bahou22a/lens-and-cataract
Secondary lens fibers (II)

• Fetal nucleus (2~8 months

gestation)
• Infantile nucleus (birth~puberty)
• Adult nucleus (secondary lens
fibers continue to form through
life)

https://www.jaypeedigital.com/eReader/chapter/9788184489804/ch1
 Lens development

• Vascular support: covered with a meshwork

of capillaries “Tunica vasculosa lentis” soon
after the lens formed
ØAnterior pupillary membrane
ØPosterior pupillary membrane (from hyaloid
artery)

https://www.aao.org/image/tunica-vasculosa-lentis-2
Remnant of tunica vasculosa lentis

https://www.slideshare.net/ArjunSapkota1/anatomy-of-lens
Persistent fetal vasculature

• Persistent hyperplastic primary

vitreous
• Rare, unilateral in 90% cases
• White, fibrous retrolenticular tissue
associated with posterior cortical
opacity
• White pupillary reflex
Development anomalies of the lens (I)

• Lenticonus is a localized, cone-shaped

deformation of the anterior or
posterior lens surface
• Posterior lenticonus is more common
than anterior lenticonus and is usually
unilateral and axial in location
• Anterior lenticonus, which is often
bilateral, may be associated with
Alport’s syndrome (nephritis, deaf )

http://www.writeopinions.com/lenticonus
Development anomalies of the lens (II)

• In lentiglobus, the localized deformation

of the lens surface is spherical
• Posterior lentiglobus is more common
than anterior lentiglobus
• Posterior lentiglobus is often associated
with posterior pole opacities that vary in
density
https://entokey.com/lens-7/
 Lens coloboma

• An anomaly of lens shape

ØPrimary coloboma, a wedge-shaped defect or indentation of the lens
periphery that occurs as an isolated anomaly
ØSecondary coloboma, caused by the lack of ciliary body or zonular
development
• Typically located inferiorly, may be associated with uveal coloboma
• Cortical lens opacification, thickening of the lens capsule, weakened or absent
zonular attachments may appear adjacent to the coloboma
 Microspherophakia

• Faulty development of the secondary lens fibers

during embryogenesis -> small in diameter and
spherical -> the entire lens equator can be
visualized when the pupil is widely dilated
• The spherical shape increases refractive power
(highly myopic) and may block the pupil
(secondary angle-closure glaucoma)
• Most often seen as a part of Weill-Marchesani syndrome
(small stature, short and stubby fingers, broad hands with
reduced joint mobility), Peters anomaly, Marfan syndrome,
Alport syndrome, Lowe syndrome, or congenital rubella https://www.nature.com/articles/jhg200975
Histology

• The Lens capsule

• The Lens epithelial cells
• The Lens fiber cells

http://www.lab.anhb.uwa.edu.au/mb140/corepages/eye/eye.htm
The Lens capsule
• A smooth, transparent basement membrane that
completely surrounds the lens
• It is synthesized by the lens epithelium
• Its main components are Type IV collagen and
sulfated glycosaminoglycans
• It is elastic enough to allow the lens to shape itself
when under the tension of the zonular fibers
• It is thickest near the equator and thinnest near
the posterior pole

http://www.lab.anhb.uwa.edu.au/mb140/corepages/eye/eye.htm
 Clinical significance

True Exfoliation
• Superficial zonular lamella of the capsule
splits off from the deep layer
• Exposure to infrared radiation induced
Pseudoexfoliation
• Basement-like fibrillgranular white
material deposited on the iris, lens capsule,
cilary processes, zonular fibers and
trabecular meshwork

https://www.slideshare.net/ArjunSapkota1/anatomy-of-lens
 The Lens epithelial cells

• It located anteriorly between the lens capsule and the lens fibers
• A simple cuboidal epithelium regulating most of the homeostatic functions of the
lens
• As nutrients enter the lens from the aqueous humor, Na+/K+-ATPase pumps pump
ions out of the lens to maintain appropriate osmotic concentration and volume
• The lens epithelium and outer cortex cells are found with the highest metabolic
rate, utilize oxygen and glucose for the active transport of electrolytes,
carbohydrates, and amino acids into the lens
• It constantly lays down fibers in the embryo, fetus, infant, and adult nucleus
 The Lens fiber cells

• The lens fibers form the bulk of the lens

• They are long, thin, transparent cells,
firmly packed fibers stretch from the
posterior to the anterior poles
• When cut horizontally, they are arranged
in concentric layers like the onion
• New lens fibers, generated from the lens
epithelium, are added to the outer
cortex
https://www.memorangapp.com/flashcards/139908/Eye+Histology/
 Zonules of Zinn

• Fibers are arises from the non-pigmented

epithelium of the ciliary body
• Anterior fibers
• Equatorial fibers
• Posterior fibers

https://www.78stepshealth.us/human-physiology/accommodation.html
Ectopia lentis (I)

• Displacement or malposition of the crystalline lens of the eye

• Simple ectopia lentis can occur as a congenital disorder or as a spontaneous
disorder later in life
• Ectopia lentis and systemic disease:
• Marfan syndrome is the most common cause of heritable ectopia lentis
Ø Ectopia lentis is the most frequent ocular manifestation (in 75% of patients)
Ø An autosomal dominant disease (various mutations to the fibrillin-1 gene located on
chromosome 15) -> altered fibrillin microfibrils -> incompetent zonular fibers and structural
abnormalities of the lens capsule

https://entokey.com/the-lens/ http://retinavitreous.com/diseases/ectopia_lentis.php
 Ectopia lentis (II)

• Homocystinuria is the second most common

cause of heritable ectopia lentis
• Lens dislocation occurs in 90% of patients
• It is associated with intellectual disability,
osteoporosis, chest deformities, and increased
risk of thrombotic episodes
• An autosomal recessive metabolic disorder most
often caused by a near absence of cystathionine
b-synthetase -> decreased zonular integrity

http://disorders.eyes.arizona.edu/disorders/homocystinuria-beta-synthase-deficiency
Physiology and Biochemistry
• Refraction: lens
*Higher refractive index (1.39) than fluid around the lens
Øhigh concentration and distribution of graded crystalline proteins in the
cytoplasm of the lens fiber cells
Øthe curvature of the lens refractive surfaces
• Accomodation:
Ø when the eye focused on near objects, the ciliary muscle constricted , the zonule relaxed -> the
lens became thicker
Ø when the ciliary muscle is relaxed, the zonule is under tension and pulls on the equatorial edge of
the lens capsule -> a thinner lens focused for distant objects
The basis of lens transparency

*The chemical composition of the lens: about 66% water; 33%

protein; and 1% lipids, salts, and carbohydrates
*Transparency
• reduced light scattering and absorption
• light pass smoothly through the lens as a result of regular structure
of lens fibers
• short range interaction between the highly concentrated crystallins
 Lens protein

α-Crystallins represent about 1/3 of the lens proteins by mass

• They are the largest of the crystallins (600 ~ 800 kDa) in their native state
• There are 2 α-crystallin subunits, αA and αB (each approximately 20 kDa), which form
heteromeric complexes containing about 30 subunits
• Bind to partially denatured proteins and prevent them from aggregating
• Their primary function: inhibit the complete denaturation and insolubilization of the other
crystallins
β-crystallins (23 to 32 kDa), a complex group of oligomers composed
of polypeptides, are encoded by 7 genes
γ-crystallins (the smallest, 20 kDa or less) is encoded by 4 genes

https://www.aao.org/image/lens-protein-2
Membrane structural proteins and
cytoskeletal proteins

• The water-soluble fraction of lens protein

• The water-insoluble fraction of lens proteins
ØThe urea-soluble fraction of the young lens contains cytoskeletal proteins that
provide the structural framework of the lens cells, microfilaments and
microtubules found in lens cells
ØThe urea-insoluble fraction of the young lens contains the plasma membranes
of the lens fiber cells, the major intrinsic protein (MIP, Aquaporin 0) makes up
nearly 50% of the membrane proteins
Increase of water-insoluble proteins with age

• As the lens ages, its proteins aggregate to form very large particles,
conversion of the water-soluble into water-insoluble proteins
Øa natural process in lens fiber maturation, but it may occur more quickly in
cataractous lenses
Øwater-insoluble proteins scatter light and increase the opacity of the lens
• Associated oxidative changes (protein-to-protein and protein-to-glutathione
disulfide bond formation) -> decreased levels of the reduced form of glutathione and
increased levels of glutathione disulfide (oxidized glutathione) in the cytoplasm of the
nuclear fiber cells
• Glutathione is essential to maintain a reducing environment in the lens
cytoplasm
 Carbohydrate metabolism
• To maintain lens transparency, energy production largely
depends on glucose metabolism
*Most of the glucose is phosphorylated to glucose-6-
phosphate (G6P) by hexokinase (rate-limited in the lens)
• Anaerobic glycolysis provides most of the high-energy
phosphate bonds required (2 ATP vs. 36 ATP for each
glucose molecule utilized in aerobic metabolism)
Ø only about 3% of the lens glucose passes through the citric
acid cycle to produce 25% of the ATP
• Hexose monophosphate (HMP) shunt: less than 5% of lens
glucose is metabolized by this route, stimulated in the
presence of elevated levels of glucose
• When glucose increases in the lens, the sorbitol pathway is
activated and sorbitol accumulates in the lens due to poor
permeability
Diabetes and cataract

https://www.sciencedirect.com/science/article/pii/B9780128094686000048
Oxidative damage and protective mechanisms
• Free radicals are generated in normal cellular metabolic activities and may be
produced by external agents such as radiant energy
Ø Free radical damage may lead to polymerization and crosslinking of lipids and
proteins -> an increase in the water-insoluble protein
• The lens is equipped with several enzymes
ØSuperoxide dismutase catalyzes the destruction of the superoxide anion
ØCatalase breaks down hydrogen peroxide
ØGlutathione peroxidase catalyzes a reaction -> glutathione disulfide, then
reconverted to glutathione by glutathione reductase
• Both vitamin E and ascorbic acid are present in the lens -> acting as a free
radical scavenger to protect against oxidative damage
 Cataracts

*Symptoms: a cataract can prevent light

from reaching the retina or cause light rays
to scatter as they pass through the
cloudiness
ØBlurry vision, double vision
ØBeing extra sensitive to light
ØHaving trouble seeing well at night
ØNeed more light when you read
ØSeeing bright colors as faded or yellow instead

https://www.aao.org/eye-health/diseases
Characteristics of lens
structures and
major types of cataracts
for location-based
classification

Liu YC, et al. Lancet 2017, 390, 600–612.

 Cataracts grading system

Types of cataract
• Cortical opacity
• Nuclear sclerosis
• Posterior subcapsular
opacity

LOCS III
What causes cataracts?

• Aging is the most common cause

• After age 40 -> increasing percentage of “insoluble” crystalline, increasing
portions of high molecular aggregates
• Family history
• Certain medical problems, such as diabetes
• History of eye injury, eye surgery, or radiation
• Frequent sun exposure, especially without sunglasses
• Using certain medications such as corticosteroids
Diagnosis

• Refraction and visual acuity test: to

assess the sharpness and clarity of
your vision
• Slit-lamp examination: to examine the
cornea, iris, lens and the other areas
at the front of the eye
• Retinal exam: to examine the back of the eye
(the retina and optic nerve)

https://www.webmd.com/eye-health/cataracts/ss/slideshow-cataracts
Cataract surgery
*Cataracts can be removed only with Surgery
• Intracapsular cataract extraction (ICCE)
• Extracapsular cataract extraction (ECCE)
• Phacoemulsification
• Laser-assisted cataract surgery
 Intracapsular cataract extraction (ICCE)

• The entire lens is removed with its capsule

• A large opening is made
• A probe is placed on the lens
Ø it is cooled using liquid nitrogen, freezing
the lens to the probe
• The lens is gently pulled out of the eye
• The wound is sealed with stitches

http://www.visualedge.org.uk/Cataracts.htm
ECCE

• https://www.slideshare.net/AbbasTelakoe/ophthalmologydiseases-of-the-lensdrbaxtyar
Phacoemulsification

*Under topical anaesthesia or retrobulbar or peribulbar anaesthesia

• A small incision in the side of the cornea with a scalpel blade
• To create a circular opening in the lens capsule (continuous curvilinear
capsulorrhexis; CCC)
• Hydrodissection (hydrdelineation)
A special probe is inserted through that opening to apply ultrasound
Øto break up the lens (emulsification) -> the broken-up pieces of lens are
suctioned (aspiration)
• An artificial intraocular lens (IOL) is implanted
• The side walls of the corneal incision is filled with BSS (self-sealed)
 Fundamentals of ultrasonic phacoemulsification (I)

• The probe delivers power both in a

longitudinal manner (moving forward
and back) and through a lateral motion
to increase cutting efficiency by
reducing repulsion of lens material
• 2 types of lateral motion:
Øtorsional: the phaco tip oscillates in a
rotational manner along its primary
axis
Øtransversal: the phaco tip moves in an
elliptical path

https://www.ypo.education/ophthalmology/micro-incisional-phacoemulsification-for-cataracts-t228/video/
Fundamentals of ultrasonic phacoemulsification (II)

• The stroke of the phaco needle creates:

Øa “mechanical impact” as the metal needle hits the cataract
Ø“cavitation” in front of the phaco needle
• A fluid and particle wave is propagated into the cataract material ->
Heat is created as a by-product
Øchoosing optimal phaco power settings to avoid burning the cornea
Øthe constant cooling effect of BSS through the surrounding irrigating sleeve
Phacoemulsification + PCIOL
Laser-assisted cataract surgery

*The femtosecond laser can take the place of procedures that

surgeons were traditionally doing manually
• To make precise corneal incisions
• To map the lens capsule better and place the opening more
precisely
Øallowing for better centering of the IOL (a premium lens, such as
an astigmatism-correcting toric IOL or a multifocal IOL)
• To break up the cataract into smaller pieces in advance
• To complete the phacoemulsification in less time
*It can improve accuracy and consistency in the surgical steps
https://www.eyedolatryblog.com/2014/09/laser-assisted-cataract-surgery-is-it.html
 IOL implants
• IOLs come in different focusing powers, just like prescription
eyeglasses or contact lenses
• Most IOLs are made of silicone or acrylic
• Monofocal IOL (one focusing distance to focus for medium
range or distance vision)
• Multifocal IOL provides both distance and near focus at the
same time (having different zones set at different powers)
• Accommodative IOL move or change shape inside the eye,
allowing focusing at different distances
• Toric IOL is designed to correct astigmatism

https://www.visivite.com/cataract-surgery-iol-choices.html
https://www.allaboutvision.com/conditions/mixed-multifocals.htm
Risks of cataract surgery

Like any surgery, cataract surgery carries risks of complications:

• Infection
• Bleeding (hyphema)
• Corneal edema
• Detached retina
• Damage to other parts of the eye
• The IOL implant dislocated
• Vision loss
Summary
• Embryology
• Histology
• Physiology and Biochemistry
• Cataracts
• Cataract Surgery
Thank you for your attention!